The goal of this project is to identify the effects of prenatal alcohol exposure on prefrontal cortical function in rats. Prenatal exposure to ethanol can produce a number of behavioral deficits in humans and animals, but the neurobiological bases underlying these deficits are not well understood. Preliminary studies in our laboratory indicate that fetal alcohol effects (FAE) in rats reduces cellular activity in the prefrontal cortex following an alternation task, as measured by c-fos mRNA induction; these animals also show a delay-dependent memory deficit in this task. These findings suggest that prenatal ethanol exposure affects the prefrontal cortex and this effect may contribute to the cognitive deficits observed in these animals. This project proposes to characterize the effect of FAE on c-fos mRNA expression in the prefrontal cortex of rats in different populations of FAE rats (gender and age) and at different time points following performance of an alternation task. In addition, this project will identify the brain circuitry involved in the cellular activation of the prefrontal cortex during alternation testing by examining c-fos mRNA expression in structures projecting to the prefrontal cortex. The effects of FAE on the mesocortical dopaminergic system innervating the prefrontal cortex and the NMDA receptor system in the prefrontal cortex will be examined using various molecular and cellular markers. The relationship of the effects of FAE on these neurobiological markers in the prefrontal cortex and on memory performance in an alternation task will be examined. Furthermore, the effects of FAE on intracellular mechanisms in prefrontal cortical neurons will be investigated on isolated cortical neurons in cell culture preparations. The findings of these studies will help identify the the effects of fetal exposure to alcohol on the prefrontal cortex and the relationship of these changes with FAE-induced cognitive deficits.